The long-term objective of this application is to characterize the chemical structures and biological activity of macrocyclic polyamine alkaloids and their precursors. These substances have been reported to exhibit antibacterial, antifungal, and antiviral activity and therefore are promising targets for the development of novel plant derived medicines. These studies are important because they will identify compounds that may successfully be used in home health care products, against a multitude of human pathogens and diseases, and possibly for the treatment of opportunistic infections that commonly occur in patients with any kind of immunosuppression. To date over 50 macrocyclic polyamine alkaloids have been described from plants, particularly of the families Celastraceae, Acanthaceae, Scrophulariaceae, Brassicaceae, a few other plant families, and several bacteria. The count does not include their synthetic analogues and numerous biological precursors. Many of these compounds have been successfully synthesized in the laboratory, which increases their potential for commercial development. The chemical structures of these substances are often based on the biogenic amines putrescine, spermidine and spermine that, in most cases are substituted with cinnamic acids to form complex macrocyclic structures. In continuation of our research program on cinnamic acid amides, we propose to elucidate the structures and test the biodynamic activity of polyamine derived alkaloids obtained from: a) greenhouse cultivated species of Lunaria and Verbascum, b) ethnobotanical plant collections of Celastraceae, Acanthaceae, and Scrophulariaceae. The ethnobotanical plant collections will be obtained in collaboration with consultants at the New York Botanical Garden. The substances will be isolated from the plant material by bioassay directed fractionation. The biological activity will be determined on cultures of several bacteria, and one fungus, and BKH cells. Quantitative assays are planned to determine the minimum inhibitory concentration (MIC) of the pure compounds. Cytotoxicity and antiviral activity of selected isolates will be determined at the Albert Einstein College of Medicine. Novel compounds will elucidated by spectroscopic methods. This research project is a joint, interdisciplinary effort by MBRS students and prime research institutions located in the Bronx including The City University of New York (Lehman College campus), The New York Botanical Garden, and the Albert Einstein College of Medicine.